pyrimidine synthesis Flashcards
what is the chemical structure of pyrimidines and what are the different types ?
contains 1 carbon ring
cytosine
thymidine
uridine
how is UMP made ?
start off with glutamine
converted to carbamoyl phosphate
into orotic acid + PRPP
and then into UMP using UMP synthase
where is TMP and CMP derived from ?
derived from UMP
what is the enzyme that catalyzes the reaction between glutamine and carbamoyl synthase ?
carbamoyl synthetase II
CPS 2
what is the difference between CPS 1 and CCPS 2 ?
CPS 1 is found in the liver and is pat of the urea cycle
CPS 2 is involved in pyrimidine synthesis and is found in most cells
what disease is associated with a dysfunction in UMP synthase ?
orotic aciduria
what other disease is commonly confused with orotic aciduria ?
OTC deficiency
what is the main difference between orotic aciduria and OTC deficiency ?
raised ammonia levels in OT defeciency
what is the treatment for orotic aciduria ?
uridine
what are the clinical features associated with orotic aciduria ?
high levels off orotic acid in urine
megaloblastic anemia
when should i suspect orotic aciduria ?
in a baby with megaloblastic anemia that is not responding too folate treatment
what are the sources of the 1 ring formation in pyrimidines ?
carbamoyl phosphate
aspartate
what drug is associated with blocking the conversion of carbamoyl phosphate to orotic acid ?
leflunomide
what is the rate limiting enzyme for CPSII ?
UMP
what enzyme is inhibited by sulphonamides ?
dihydropteroate synthase this is in bacteria
what enzyme is inhibited by trimethoprim ?
dihydrofolate reductase this is in bacteria
what drug blocks human dihydrofolate reductase ?
methotrexate
by lab workup how can you differentiate between folate and vitamin b12 deficiency ?
both have a high level of homocystenuria
but there is a higher level of MMA in B12 deficiencies
what is the clinical presentation of both b12 and folate deficiencies ?
folate - macrocytic anemia, neural tube defects
b12 - macrocytic anemia , neurological dysfunction ( causes demyelination )
what is the role of folate in thee conversion of uridine into thymidine ?
N5. abd N10 tetrahydrofolate levels must be maintained iin order for the conversion to happen
what is the other common phrase used to describe folate ?
1 carbon carrier
what enzyme is blocked by the drug 5 FU ?
thymidlate synthase
what enzyme is blocked by methotrexate ?
dihydrofolate reductasea
how does 5 FU work as a chemotherapeutic agent ?
it mimics uracil
makes an abnormal dUMP
so no thymine is produced for cancer cells
what are the sources of the 1 ring found in pyrimidines ?
carbamoyl phosphate and aspartate
what enzyme is inhibited by the drug hydroxyurea ?
ribonucleotide redutase
what enzyme is inhibited by leflunomide ?
dihydroorotate dehydrogenase
what is the prodrug for 5 FU and what is the enzyme inhibited by this drug ?
capectabine
thymidylate synthase
what are the after effects of giving azathioprine with another xanthine oxidase inhibitor ?
immunosuppression
what enzyme is blocked by mycophenolate and ribavarin ?
inosine monophosphate dehydrogenase
what enzyme is inhibited by cytosine arabinoside ?
DNA polymrase
what turns UMP into dUMP ?
ribonucleotide reductase
what diseases are treated hydroxyurea ?
polycythemia vera
essential thrombocytosis
sickle cell anemia
what reaction does CPSII facilitate ?
glutamine to carbamoyl phosphate
CPSII stands for carbamoyl synthetase
CPS1 vs CPS11 ?
cps1 is purely mitochondria ( hepatic )
cps2 is purely cytosolic
in the pyrimidine synthesis process what process is inhibited by methotrexate and azathioprine ?
the conversion of PRPP to IMP
